American Journal of Advanced Drug Delivery
www.ajadd.co.uk
Original Article Nitrofurantoin in Urinary Tract Infection: Old is Gold Jayashree Konar, Indrani Bhattacharyya*, Sipra Saha, Dipankar Paul, Sourav Maiti and Gargi Bhattacharya
Department of Microbiology, Calcutta School of Tropical Medicine, Kolkata
Date of Receipt- 16/6/2014 ABSTRACT Date of Revision- 19/6/2014 Date of Acceptance- 28/6/2014 Objective of the study was to find out the Resistogram of the urinary
isolates against different commonly prescribed antimicrobials according to CLSI guidelines. Out of total 319 test samples, in 56 cases bacterial pathogens were isolated. Among those 56 isolates only 13 were resistant to Nitrofurantoin (23.21%) where as resistance to Ciprofloxacin was found in 40 isolates(71.42%), resistance against Co Trimoxazole was found in 27 isolates (48.21%) and surprisingly, resistance against Carbapenem antibiotics (Meropenem) was in 20 isolates (35.71%). Majority of the Nitrofurantoin resistant bacterial isolates were Klebsiella pneumoniae (4 out of 13 i.e, 30.76%). All Nitrofurantoin resistant isolates were sensitive to both Tigecycline Address for and Colistin and the isolated Escherichia coli (two in number) were Correspondence sensitive to Meropenem also. There were no other therapeutic options Department of like Fluroquinolones or Co trimoxazole to manage the Nitrofurantoin Microbiology, Calcutta resistant isolates as all of them were resistant to them. Thus medical School of Tropical community should think twice before replacing Nitrofurantoin with Medicine, Kolkata Fluroquinolones or Co Trimoxazoles as emperical therapy. E-mail: indranichaudhuri Keywords : Emperical Therapy, Nitrofurantoin, Resistogram, @yahoo.com Sensitive, UTI.
INTRODUCTION Urinary tract infection (UTI) is one by damaging bacterial DNA, since its of the most common health problems in the reduced form is highly reactive. Organisms community as well as in nosocomial set up 1 are said to be susceptible to nitrofurantoin if 5. It is almost impossible to find out a their minimum inhibitory concentration clinician who has never attended & treated (MIC) is 32 g/mL or less. The peak blood at least one case of UTI throughout his concentration of nitrofurantoin following an career. Nitrofurantoin is an age old drug to oral dose of 100 mg, is less than 1 g/mL treat uncomplicated UTI 6 9. The drug works and may be undetectable; tissue penetration
American Journal of Advanced Drug Delivery www.ajadd.co.uk Bhattacharyya et al______ISSN 2321-547X is negligible; the drug is well concentrated Bauer disk diffusion technique according to in the urine. At the concentrations achieved CLSI guidelines. in urine (>100 µg/mL), nitrofurantoin is bacteriocidal. It is bacteriostatic against RESULTS AND DISCUSSION most susceptible organisms at concentrations less than 32 g/mL 10 . Out of total 319 test samples, in 56 Nitrofurantoin and the quinolone cases bacterial pathogens were isolated. antibiotics are mutually antagonistic in vitro . Among those 56 isolates only 13 were It is not known whether this is of clinical resistant to Nitrofurantoin (23.21%) where as significance, but the combination should be resistance to Ciprofloxacin was in 40 isolates avoided 11 . (71.42%), resistance against Co Trimoxazole Now a days, different guidelines are was in 27 isolates (48.21%) and surprisingly, giving emphasis on Fluroquinolones and resistance against Carbapenem antibiotics Co trimoxazole 10 17 . Again, Carbapenems (Meropenem) was in 20 isolates (35.71%). inspite of being a parenteral option, are also Majority of the Nitrofurantoin prescribed by several schools. However, this resistant bacterial isolates were Klebsiella study reveals the fact that bacterial isolates pneumoniae (4 out of 13 i.e, 30.76%). developed greater resistance against Distribution of Nitrofurantoin resistant Fluroquinolones, Co trimoxazole and isolates are depicted in following Bar Carbapenems more than Nitrofurantoin. diagram. See Fig. 1. OBJECTIVE All Nitrofurantoin resistant isolates were sensitive to both Tigecycline and Objective of the present study was to Colistin and the isolated Escherichia coli (two find out the sensitivity pattern of the urinary in number) were sensitive to Meropenem isolates against different commonly also. There were no other therapeutic options prescribed antimicrobials in uncomplicated like Fluroquinolones or Co trimoxazole to UTI. manage the Nitrofurantoin resistant isolates as all of them were resistant to them. MATERIALS AND METHODS DISCUSSION The study was performed from Jauary 2014 to February 2014 with 319 suspected Nitrofurantoin is a cost effective oral patients with signs and symptoms of drug with good patient compliance 18 20 . uncomplicated UTI. Urinary urgency, Within its therapeutic range it has no grave hesitancy, increased frequency of micturition , adverse effect 21 .24 . The present study pyrexia and burning sensation during establishes the fact that majority of the micturition were the symptoms to fulfill the organisms causing uncomplicated UTI are inclusion criteria. Immunocompromised sensitive to it be it a gram positive one or a patients, patients with renal transplantation gram negative one. Among 56 isolates only and any other co morbidity were excluded 13 were resistant to Nitrofurantoin (23.21%) from the study.Microbiological work up to where as resistance to Ciprofloxacin was in isolate and identify the bacterial pathogen 40 isolates(71.42%), resistance against Co from mid stream urine collected in proper Trimoxazole was in 27 isolates (48.21%) and sterile manner was done as per standard surprisingly, resistance against Carbapenem protocol. Antibiogram was done by Kirby antibiotics (Meropenem) was also high i.e, in 20 isolates (35.71%).These findings in our
AJADD[2][4][2014]463-467 Bhattacharyya et al______ISSN 2321-547X antimicrobial resistogram corroborates with 4. Hummers Pradier E, Denig P, Oke T, the work of Awari et al 25 . Lagerløv P, Wahlström R, Haaijer There is a scarcity of data in medical Ruskamp FM. GPs' treatment of literature about the sensitivity of gram uncomplicated urinary tract infections a positive organisms to Nitrofurantoin. clinical judgement analysis in four However in the study of Bhattacharyya et al . European countries. DEP group. Drug in Kolkata, no Nitrofurantoin resistant Education Project. Fam Pract . 1999 Enterococcus sp. was reported, two Dec;16(6):605–607. intermediately sensitive Enterococcus spp. 5. Huang Elbert S, Stafford Randall S. were reported (determined by VITEK 2 AES National patterns in the treatment of system) 26 . Similarly in this study, majority of urinary tract infections in women by the Nitrofurantoin resistant bacteria were ambulatory care physicians. Arch Intern gram negative ( Klebsiella pneumoniae Med. 2002 Jan 14;162(1):41–47. 30.76%) and only one gram positive bacteria 6. Zalmanovici Trestioreanu A, Green H, (Enterococcus sp.) was found to be resistant. Paul M, Yaphe J, Leibovici L. Antimicrobial agents for treating CONCLUSION uncomplicated urinary tract infection in women. Cochrane review. in Cochrane Nitrofurantoin inspite of being an Database Syst Rev. 2010 Oct older option can be used in pregnancy 6;(10):CD007182. espescially in early trimesters whereas 7. Lutters M, Vogt N. Antibiotic duration opinion about Cotrimoxazole and for treating uncomplicated, symptomatic Ciprofloxacin are controversial. Thus medical lower urinary tract infections in elderly community should think twice before totally women. Cochrane Database Syst Rev. replacing Nitrofurantoin with 2002;(3):CD001535–CD001535. Fluroquinolones or Co Trimoxazole as 8. Jellheden B, Norrby RS, Sandberg T. emperical therapy. Symptomatic urinary tract infection in women in primary health care. REFERENCES Bacteriological, clinical and diagnostic aspects in relation to host response to 1. Verest LF, van Esch WM, van Ree JW, infection. Scand J Prim Health Care. Stobberingh EE. Management of acute 1996 Jun;14(2):122–128. uncomplicated urinary tract infections in 9. Melekos MD, Naber KG. Complicated general practice in the south of The urinary tract infections. Int J Antimicrob Netherlands. Br J Gen Pract . 2000 Agents. 2000 Aug;15(4):247–256. Apr;50(453):309–310. 10. "Macrobid Drug Label". FDA. Retrieved 2. Wigton RS, Longenecker JC, Bryan TJ, 21 April 2014. Parenti C, Flach SD, Tape TG. Variation 11. Colgan R, Williams M. Diagnosis and by specialty in the treatment of urinary Treatment of Acute Uncomplicated tract infection in women. J Gen Intern Cystitis. Am Fam Physician . 2011 Oct Med . 1999 Aug;14(8):491–494. 1;84(7):771 6. 3. Olesen F, Oestergaard I. Patients with 12. Barnett BJ, Stephens DS. Urinary tract urinary tract infection: proposed infection: an overview. Am J Med Sci. management strategies of general 1997 Oct;314(4):245–249. practitioners, microbiologists and urologists. Br J Gen Pract . 1995 Nov;45(400):611–613.
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13. Ross AM. UTI antimicrobial resistance: 20. FishmanN. Antimicrobial stewardship. tricky decisions ahead? Br J Gen Pract . Am. J Med 2006;119 6 Suppl 1:S53 61. 2000 Aug;50(457):612–613. 21. Veninga CC, Lundborg CS, Lagerløv P, 14. Gupta K, Hooton TM, Stamm WE. Hummers Pradier E, Denig P, Haaijer Increasing antimicrobial resistance and Ruskamp FM. Treatment of the management of uncomplicated uncomplicated urinary tract infections: community acquired urinary tract exploring differences in adherence to infections. Ann Intern Med . 2001 Jul guidelines between three European 3;135(1):41–50. countries. Drug Education Project 15. Schultz HJ, Edson RS. Cystitis Group. Ann Pharmacother. 2000 Treatment in Women, Circa 2011: New Jan;34(1):19–26. Role for an Old Drug. Mayo Clin Proc. 22. Crider KS, Cleves MA, Reefhuis J, 2011 Jun;86(6):477 9. Berry RJ, Hobbs CA,Hu DJ. 16. McCarty JM, Richard G, Huck W, Antibacterial medication use during Tucker RM, Tosiello RL, Shan M, Heyd pregnancy and risk of birth defects: A, Echols RM. A randomized trial of National Birth Defects Prevention Study. short course ciprofloxacin, ofloxacin, or Arch Pediatr Adolesc Med trimethoprim/sulfamethoxazole for the 2009;163:978–85. treatment of acute urinary tract infection 23. Drug Safety Update by MHRA. August in women. Ciprofloxacin Urinary Tract 2013,Volume 7, Issue 1, A3. Infection Group. Am J Med . 1999 24. Leão RN, Barreto P, Leão RR, Ribeiro Mar;106(3):292–299. JV. Nitrofurantoin: cause of DRESS 17. Barber AE, Norton JP, Spivak AM, syndrome. BMJ Case Rep. 2013 Mulvey MA.Urinary Tract Infection: 25. Abhijit Awari, Sunita Nighute, Maria Current and Emerging Management Khatoon. Study of urinary isolates with strategies. Clin Infect Dis. 2013 reference to extended spectrum beta Sep;57(5):719 24. lactamases detection and antibiogram. 18. Cunha BA, Schoch PE, Hage JR Mayo. Journal of Evolution of Medical and Nitrofurantoin: in Preferred Empiric Dental Sciences .;2013 Volume 2, Issue Therapy for Community Acquired 9: Page1049 1055. Lower Urinary Tract Infections. Clin 26. Indrani Bhattacharyya, Jayashree Konar, Proc . 2011 Dec;86(12):1243 4 Sanjeev Das, Pratip Kumar Kundu, Md. 19. William A. Richards, Egon Riss, Edward Samidul Hoque. “Old wine in a new h. Kass, maxwell Finland. Nitrofurantoin bottle – enterococcal urinary tract Clinical and Laboratory Studies in infection in nosocomial setup”. Journal Urinary Tract Infections. AMA Arch of Evolution of Medical and Dental Intern Med. 1955;96(4):437 450. Sciences 2013; Vol. 2, Issue 43, October 28;Page:8277 8283.
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Fig. 1. Distribution of Nitrofurantoin resistant .
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